rs470119

Variant names:

• chr22-50528485-T-C
• rs470119
• NM_001953.5:c.516+27A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-50528485-T-C
• chr22-50528485-T-A
• chr22-50528485-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001953.5(TYMP):​c.516+27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,590,248 control chromosomes in the GnomAD database, including 296,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24204 hom., cov: 32)
  • Exomes 𝑓: 0.61 (271880 hom.)
• Consequence: TYMP NM_001953.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.821
• Publications: 70 publications found

Genes affected

TYMP (HGNC:3148): (thymidine phosphorylase) This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2012]

TYMP Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial DNA depletion syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• mitochondrial neurogastrointestinal encephalomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-50528485-T-C is Benign according to our data. Variant chr22-50528485-T-C is described in ClinVar as Benign. ClinVar VariationId is 671618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001953.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYMP	NM_001953.5	MANE Select	c.516+27A>G		intron	N/A	NP_001944.1	E5KRG5
	TYMP	NM_001257989.1		c.516+27A>G		intron	N/A	NP_001244918.1	P19971-2
	TYMP	NM_001113755.3		c.516+27A>G		intron	N/A	NP_001107227.1	E5KRG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYMP	ENST00000252029.8	TSL:1 MANE Select	c.516+27A>G		intron	N/A	ENSP00000252029.3	P19971-1
	TYMP	ENST00000395681.6	TSL:1	c.516+27A>G		intron	N/A	ENSP00000379038.1	P19971-2
	TYMP	ENST00000395678.7	TSL:1	c.516+27A>G		intron	N/A	ENSP00000379036.3	P19971-1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83688 AN: 151942 Hom.: 24209 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.560

GnomAD2 exomes AF: 0.615 AC: 149977 AN: 243934 AF XY: 0.621

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.697

Gnomad FIN exome AF: 0.654

Gnomad NFE exome AF: 0.608

Gnomad OTH exome AF: 0.627

GnomAD4 exome AF: 0.612 AC: 880749 AN: 1438188 Hom.: 271880 Cov.: 25 AF XY: 0.615 AC XY: 440451 AN XY: 716548

African (AFR) AF: 0.346 AC: 11455 AN: 33092

American (AMR) AF: 0.630 AC: 27712 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 16672 AN: 25852

East Asian (EAS) AF: 0.718 AC: 28384 AN: 39518

South Asian (SAS) AF: 0.677 AC: 57580 AN: 85050

European-Finnish (FIN) AF: 0.644 AC: 34026 AN: 52852

Middle Eastern (MID) AF: 0.690 AC: 3947 AN: 5718

European-Non Finnish (NFE) AF: 0.609 AC: 665007 AN: 1092474

Other (OTH) AF: 0.603 AC: 35966 AN: 59652

GnomAD4 genome AF: 0.550 AC: 83701 AN: 152060 Hom.: 24204 Cov.: 32 AF XY: 0.559 AC XY: 41541 AN XY: 74330

African (AFR) AF: 0.360 AC: 14943 AN: 41470

American (AMR) AF: 0.617 AC: 9420 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2296 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3673 AN: 5170

South Asian (SAS) AF: 0.663 AC: 3199 AN: 4824

European-Finnish (FIN) AF: 0.660 AC: 6983 AN: 10578

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.607 AC: 41265 AN: 67968

Other (OTH) AF: 0.557 AC: 1175 AN: 2110

Alfa AF: 0.592 Hom.: 85032

Bravo AF: 0.540

Asia WGS AF: 0.607 AC: 2113 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Mitochondrial DNA depletion syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.43
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs470119; hg19: chr22-50966914;